1. Field
The present invention relates to a method of manufacturing a microneedle.
2. Description of the Related Art
Percutaneous absorption has been known as one of the methods for administering a drug by permitting it to permeate through the skin. This method is noninvasive, and makes it possible to simply administer the drug without giving pain to the human body. However, administration by percutaneous absorption may be difficult depending on the kind of the drug.
Accordingly, a noticed method is to directly inject the drug beneath the skin by perforating the skin using a microneedle array having many needles of micron order in order to permit the drug to be efficiently absorbed into the body. This method enables simple subcutaneous administration without using any special devices (see U.S. Pat. No. 6,183,434).
The microneedle is required to have sufficient fineness and point angle for piercing the skin, and a sufficient length for permitting the drug solution to be permeated under the skin. The diameter of the needle is desirably in the range of several μm to several hundred μm. The needle desirably has a length enough for penetrating the corneal layer as the outermost layer of the skin. While the thickness of the corneal layer differs depending on the site of the body, it is about 20 μm on average. The epidermis is laid under the corneal layer with a thickness of about 200 μm to about 350 μm, and the dermic layer in which capillary vessels are extended is laid under the epidermis. Accordingly, at least 20 μm or more of the length of the needle is necessary for allowing the needle to penetrate the corneal layer in order to permit the drug solution to permeate. A needle length of at least 350 μm or more is necessary for sampling the blood.
Usually, the microneedle has been attempted to be manufactured by processing silicon. Silicon is a material widely used for manufacturing MEMS devices and semiconductors, and is cheap and excellent in fine processability. A method proposed for manufacturing a silicon microneedle includes the steps of: patterning a silicon oxide film formed on both surfaces of a silicon wafer; applying crystal anisotropy etching from the surface of the wafer; and applying isotropic etching from the back surface of the wafer. For example, a microneedle with a length of 500 μm or more and a width of 200 μm or less may be manufactured by this method. Sampling of the blood is further secured by forming an array of such microneedles (see Jpn. Pat. Appln. KOKAI Publication No. 2002-369816). Likewise, another proposed manufacturing method includes the steps of: subjecting a silicon substrate to wet etching; and forming the microneedle by taking advantage of a difference in the etching rate among crystal orientations of a silicon single crystal material (see Jpn. Pat. Appln. KOKAI Publication No. 2004-58265).
Methods for manufacturing the microneedle using materials other than silicon have been also proposed. For example, the microneedles are formed by a wire cutting method on one surface of a processed steel plate. The size and shape of the microneedle formed are controlled by changing downward and upward cutting angles (see Jpn. PCT National Publication No. 2006-513811).
The material constituting the microneedle is required to be harmless to the human body even when the microneedle is broken and left behind in the body. Examples of the material that is considered to be promising include a biocompatible material such as a medical silicone resin, maltose, polylactic acid and dextran (see Jpn. Pat. Appln. KOKAI Publication No. 2005-21677).
A transcription molding method represented by injection molding, imprinting and casting is effective for manufacturing these fine structures with a low cost in large scale. However, since a master plate having an inversed shape of desired recessed and projected portions is necessary for molding by any of these methods, the manufacturing process becomes quite complicated for forming a structure having a high aspect ratio (the ratio of height or depth to width of the structure) and a sharp tip as the microneedle.
Since the method using wet etching in the related art takes advantage of a difference in etching rates among orientations of the crystal plane, a highly purified single crystal material is necessary for manufacturing the microneedle. The taper angle and point angle of the microneedle is determined by the property of the single crystal material. Accordingly, it is difficult to manufacture the microneedle by designing an appropriate shape and size of the microneedle while taking the constitution of the skin into consideration.
Since it is impossible to shift upward cutting to downward cutting immediately after upward cutting has reached the apex of the microneedle in the method using wire cutting, horizontal cutting actually advances for a length from 1 to 20 μm. Consequently, the microneedle manufactured has a trapezoidal cone shape having a flat plane on the apex of the needle, and the performance for piercing with the microneedle is impaired.
Generally, columnar or conical needles are aligned upright on the surface of the flat substrate in the microneedle aligned in an array. However, the side surface of the microneedle becomes to have a sharp corner with the surface of the substrate at the base of the microneedle in the manufacturing method in the related art. A stress is converged on the corner portion at the base of the microneedle when the microneedle is shaped as described above, and the microneedle may be broken by piercing.